At present, urokinase separated and purified from urine or cultured liquor of kidney cells and streptokinase collected from cultured liquor of Streptococci are plasminogen activators employed in practical use as thrombolytic agents.
However, since urokinase and streptokinase possess poor affinity to fibrin, it is frequently necessary to administer them in large amounts in order to obtain the required effect on treatment. When large doses are administered, side effects such as gastro-internal hemorrhage are manifested. Under such circumstances, a thrombolytic agent having thrombolyzing activity when administered in a small dose and having only a low level of side effects such as causing an gastro-internal hemorrhage has been eagerly sought.
In recent years, a plasminogen activator separated and purified from a tissue cultured liquor of human melanoma cells has been proposed to serve similar purposes (see Japanese Patent Application (OPI) No. 28009/1982). However, since tumor cells are used as a starting material and these are problems with antigenicity and carcinogenicity, such a plasminogen activator cannot be presented for practical use.
The present inventors have discovered, as the result of their study on various tissue cultured liquors of human normal tissue derived cells, that a substance having plasminogen activator activity different from urokinase is contained therein, and they are successfully separated and purified it, thereby having accomplished this invention.
The plasminogen activator of this invention is separated from a tissue cultured liquor of normal tissue derived cells and thus does not have the above-described drawbacks of the plasminogen activator derived from melanoma cells.